RGD Reference Report - RIM proteins activate vesicle priming by reversing autoinhibitory homodimerization of Munc13. - Rat Genome Database

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RIM proteins activate vesicle priming by reversing autoinhibitory homodimerization of Munc13.

Authors: Deng, L  Kaeser, PS  Xu, W  Sudhof, TC 
Citation: Deng L, etal., Neuron. 2011 Jan 27;69(2):317-31. doi: 10.1016/j.neuron.2011.01.005.
RGD ID: 10047275
Pubmed: PMID:21262469   (View Abstract at PubMed)
PMCID: PMC3063404   (View Article at PubMed Central)
DOI: DOI:10.1016/j.neuron.2011.01.005   (Journal Full-text)

At a synapse, the presynaptic active zone mediates synaptic vesicle exocytosis. RIM proteins are active zone scaffolding molecules that--among others--mediate vesicle priming and directly or indirectly interact with most other essential presynaptic proteins. In particular, the Zn(2)+ finger domain of RIMs binds to the C(2)A domain of the priming factor Munc13, which forms a homodimer in the absence of RIM but a heterodimer with it. Here, we show that RIMs mediate vesicle priming not by coupling Munc13 to other active zone proteins as thought but by directly activating Munc13. Specifically, we found that the isolated Zn(2)+ finger domain of RIMs autonomously promoted vesicle priming by binding to Munc13, thereby relieving Munc13 homodimerization. Strikingly, constitutively monomeric mutants of Munc13 rescued priming in RIM-deficient synapses, whereas wild-type Munc13 did not. Both mutant and wild-type Munc13, however, rescued priming in Munc13-deficient synapses. Thus, homodimerization of Munc13 inhibits its priming function, and RIMs activate priming by disrupting Munc13 homodimerization.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
plasma membrane located_inIGIUniProtKB:Q62769-110047275PMID:21262469ParkinsonsUK-UCL 
plasma membrane located_inIGIUniProtKB:Q9JIR410047275PMID:21262469ParkinsonsUK-UCL 
terminal bouton located_inIGIUniProtKB:Q99NE5 and UniProtKB:Q9EQZ710047275PMID:21262469ParkinsonsUK-UCL 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:Q62769-110047275PMID:21262469ParkinsonsUK-UCL 
protein binding enablesIPIUniProtKB:Q9JIR410047275PMID:21262469ParkinsonsUK-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Rims1  (regulating synaptic membrane exocytosis 1)
Unc13b  (unc-13 homolog B)


Additional Information